Biomedical subjects

H Hamada

Publications and source records attributed to H Hamada.

At least 613 records · Page 34Linked to original sources

PubMedDate not supplied

Is there a correlation between cardiac sympathetic neuropathy or diabetic somatic neuropathy and glycosylated haemoglobin or blood pressure in patients with non-insulin-dependent diabetes mellitus?

The possibility that glycosylated haemoglobin levels and/or blood pressure might correlate with cardiac sympathetic neuropathy and/or diabetic somatic neuropathy was investigated in patients with non-insulin-dependent diabetes mellitus. Sympathetic nerve function was quantified by analysis of [123I]metaiodobenzylguanidine accumulation in the cardiac muscle. Somatic nerve function was assessed by measuring the motor nerve conduction velocities of the peroneal and tibial nerves, and the sensory nerve conduction velocity of the sural nerve. None of the parameters of cardiac sympathetic neuropathy or diabetic somatic neuropathy showed any correlation with blood pressure, nor was there any evidence of a correlation between cardiac sympathetic neuropathy and glycosylated haemoglobin levels; there was, however, a significant correlation between diabetic somatic neuropathy (as indicated by tibial nerve conduction velocity) and glycosylated haemoglobin levels. The results are consistent with the view that different mechanisms are involved in the two types of neuropathies.

3-Iodobenzylguanidine↗

PubMedDate not supplied

Can alpha-glucosidase inhibitors reduce the insulin dosage administered to patients with non-insulin-dependent diabetes mellitus?

For 10 patients (three women and seven men) with noninsulin-dependent diabetes mellitus, who had been given insulin (22.6 +/- 19.6 U/day) and had frequently shown hypoglycaemia, the insulin dose was slightly reduced and the administration of an alpha-glucosidase inhibitor was simultaneously started. Hypoglycaemic symptoms disappeared immediately and completely, and sugar metabolism immediately before the withdrawal of treatment was not aggravated: the glycosylated haemoglobin level was unchanged and the post-prandial blood glucose level was increased though not significantly. The results of the present study indicate that the combined used of an alpha-glucosidase inhibitor with a reduced insulin dose improves the quality of life of patients and may improve hyperinsulinaemia.

Blood Glucose↗

PubMedDate not supplied

Effect of alpha-glucosidase inhibitor in combination with sulphonylurea compounds on lipid profile in patients with non-insulin-dependent diabetes mellitus.

The effects of administration of an alpha-glucosidase inhibitor and a sulphonylurea compound on lipid profile were investigated in patients with non-insulin-dependent diabetes mellitus, (NIDDM) previously treated with sulphonylurea compounds alone, but in whom metabolic control was inadequate. A group of patients (n = 10) were treated with the alpha-glucosidase inhibitor at a dose of 0.2 mg, three times daily, for 4 weeks. Treatment significantly reduced the post-prandial glucose level and the serum total cholesterol level. In addition, there were non-significant reductions in the triglyceride and very low density lipoprotein levels. These preliminary results suggest that administration of alpha-glucosidase inhibitors might improve the lipid profile of patients with NIDDM.

Blood Glucose↗

PubMedDate not supplied

Insulin secretion levels necessary for efficacy of an alpha-glucosidase inhibitor on glucose metabolism in patients with non-insulin-dependent diabetes mellitus.

Twenty patients with non-insulin-dependent diabetes mellitus whose glucose metabolism was unsatisfactory, even though they were receiving appropriate dietary therapy, were treated with an alpha-glucosidase inhibitor (0.6 mg/day) for 12 weeks. The connecting peptide immunoreactivity value (selected as the evaluation criterion of post-prandial endogenous insulin secretion) was compared in patients with and without improved glycosylated haemoglobin levels. A significant difference was found between the connecting peptide immunoreactivity value of the group with improved glycosylated haemoglobin levels (5.0 +/- 1.0 ng/ml) and that in the group without the improvement (2.7 +/- 0.9 ng/ml).

Blood Glucose↗

PubMedDate not supplied

Can alpha-glucosidase inhibitors reduce the dosage of sulphonylurea compounds needed by patients with non-insulin-dependent diabetes mellitus?

The effects of treatment with an alpha-glucosidase inhibitor and a reduced dose of sulphonylurea were investigated in patients with non-insulin-dependent diabetes mellitus who had previously been treated with sulphonylurea compounds but who were hypoglycaemic at times. Treatment with a daily dose of 0.6 mg alpha-glucosidase inhibitor and a reduced dose of the previously used sulphonylurea compound for 4 weeks did not significantly affect the glycosylated haemoglobin level. The post-prandial blood-glucose concentration of the patients was unchanged after treatment compared with its value immediately before treatment but differed significantly compared with the value 4 weeks before treatment (P < 0.03); it was considered likely that this change was due to a seasonal increase in calorie intake at the end of the treatment period. Symptoms related to hypoglycaemia disappeared in all of the treated patients.

Diabetes Mellitus, Type 2↗

PubMedDate not supplied

Estimated urinary albumin index: a predictor of microalbuminuria in type 2 diabetes.

This study examined factors contributing to the development of microalbuminuria in diabetic patients. A total of 236 patients with Type 2 diabetes were studied: 143 were normoalbuminuric and 86 were also normotensive. Multiple regression analysis was used to identify factors influencing the urinary albumin index (UAI), an index of proteinuria based on urinary albumin adjusted for urinary creatinine. Significant factors (retinopathy, systolic blood pressure, and glycosylated haemoglobin) were used to generate a formula for estimating the log(e) UAI. Target values for systolic blood pressure and glycosylated haemoglobin to maintain the urinary albumin index at or below 22 were determined for different degrees of retinopathy. Normoalbuminuric patients were followed for 3 years to evaluate their progression to microalbuminuria. Each month, blood pressure, urinary albumin and creatinine, and glycosylated haemoglobin were measured. In normotensive, normoalbuminuric patients, initial urinary albumin index and log(e) UAI were significantly higher in patients who subsequently developed microalbuminuria. Patients with initial log(e) UAI > 3.09 or initial glycosylated haemoglobin > 6.0% also showed greater progression to microalbuminuria. Hyperglycaemia was an independent factor for the development of microalbuminuria in Type 2 diabetes. The urinary albumin index was most significantly affected by retinopathy, systolic blood pressure, and glycosylated haemoglobin. The estimated loge UAI calculated from these factors is a useful predictor of progression to microalbuminuria.

Adolescent↗

PubMedDate not supplied

Relationship between cardiac autonomic neuropathy and diabetic microangiopathies and macroangiopathy in patients with non-insulin-dependent diabetes mellitus.

The relationship between cardiac autonomic neuropathy and diabetic microangiopathies and macroangiopathy was investigated in 103 patients with non-insulin-dependent diabetes mellitus. Cardiac autonomic nerve function was assessed by determining the uptake of [123I]metaiodobenzyl-guanidine into the myocardium. Cardioparasympathetic nerve function was assessed by comparing electrocardiographically the expiratory and inspiratory respiratory rate (RR) interval ratios, during a period of deep breathing, and the coefficients of variation of the RR intervals. Nerve conduction velocity measurements were used to assess diabetic somatic neuropathy, and measurement of pulse-wave velocity provided an indication of the extent of aortic sclerosis. The only correlations between the parameters of cardiac autonomic neuropathy and parameters of diabetic microangiopathies and macroangiopathy were between the expiratory to inspiratory RR interval ratio and both the conduction velocity of the tibial nerve and pulse-wave velocity, and between the heart to lung ratio (cardiac autonomic nerve function) and nephropathy. These correlations may have occurred by chance; alternatively they may indicate a difference in the onset mechanisms of cardiac parasympathetic and sympathetic neuropathies in diabetics.

Aged↗

PubMedDate not supplied

Significance of metabolic and blood pressure factors in relation to microangiopathy and macroangiopathy in patients with non-insulin-dependent diabetes mellitus.

We are actively seeking methods to prevent and to limit the progression of angiopathy in patients with non-insulin-dependent diabetes mellitus (NIDDM). In the present study, we conducted a clinical and epidemiological survey to clarify the clinical factors responsible for the development and progression of diabetic microangiopathy (MI) and macroangiopathy (MA). A total of 107 patients (58 female and 49 male) were randomly selected from 145 NIDDM patients. Twenty-four patient variables were selected for analysis. We identified PWV, UAI, RETINOP, MCV-T, SCV-S, MCV-P, SBP, and DBP as responsible factors and carried out stepwise multiple regression analyses. The following explanatory variables were found to be significant: age > SCV-S (P < 0.0001) for the criterion variable PWV, BUN > HbA1c > MCV-P > HT-drug > HDL-C (P < 0.0001) for log(e) UAI, DM-thera > SBP (P < 0.0001) for RETINOP, MCV-P (P < 0.0001) for MCV-T, IRI > SBP > MCV-P > S-CR (P < 0.0002) for SCV-S, MCV-T > SCV-S > DM-thera (P < 0.0001) for MCV-P, DBP > HT-drug > BUN > MCV-P (P < 0.0001) for SBP, and SBP > PWV > sex (P < 0.0001) for DBP. In summary, responsible factors for MI and MA in NIDDM had metabolic and blood pressure factors in common. Moreover, MI was a responsible factor for MA, which becomes a responsible factor for MI because it is a responsible factor for blood pressure factors. Thus, all the responsible factors for MA represented by MI and PWV had metabolic and blood pressure factors in common. The results of this study suggest that metabolic and blood pressure factors must be controlled to prevent and to limit the progression of diabetic MI and MA in NIDDM patients.

Adolescent↗

PubMedDate not supplied

Diversity of the neuropathies in patients with non-insulin-dependent diabetes mellitus.

The relationships between cardiac autonomic neuropathies, diabetic somatic neuropathy, metabolic parameters, general parameters (such as age and duration of illness) and diabetic microangiopathy and macroangiopathy were investigated in 103 patients with non-insulin-dependent diabetes mellitus (NIDDM). Spearman's correlation coefficients were calculated for the comparisons of all the parameters of the neuropathies with all the other parameters. Variables were selected using a stepwise procedure and multiple regression analysis was carried out using these variables. The results of the regression analysis show that diabetic neuropathy is correlated with vascular parameters including blood pressure and pulse-wave velocity, as well as with parameters of sugar and lipid metabolism. The results confirm the diversity of the clinical characteristics of the neuropathies in patients with NIDDM and confirm that these neuropathies do not always occur in parallel.

Aged↗

PubMedDate not supplied

Use of an alpha-glucosidase inhibitor to synchronize sugar absorption with delayed insulin secretion in a patient with non-insulin-dependent diabetes mellitus.

The case of a 67-year-old women with non-insulin-dependent diabetes mellitus is described. Diabetes was first diagnosed when the woman was aged 55; a diet of 1440 kcal daily was recommended and 500 mg tolbutamide daily was prescribed. Hypoglycaemia was improved for a while but the blood-sugar concentration gradually increased until a tolbutamide dose of 2000 mg/day was needed. The patient eventually came to an out-patient clinic for diabetes control due to continuous hyperglycaemia. Her diabetes proved difficult to control, probably due, in part, to excessive eating and lack of exercise, despite appropriate education and glibenclamide treatment. After 15 months, an alpha-glycosidase inhibitor, at a dosage of 0.75 mg/day, was added to the treatment with glibenclamide at 7.5 mg/day and the glycosylated haemoglobin level was reduced to normal levels within 2 months. After a further 6 months the glibenclamide dose was reduced to 3.75 mg/day with no ill effects during the subsequent 4 weeks, up to the present day.

Aged↗

PubMedDate not supplied

Factors related to the development and progression of diabetic retinopathy in patients with type 2 diabetes.

This study was intended to clarify the factors associated with the development and progression of diabetic retinopathy in patients with Type 2 diabetes. A total of 107 patients with Type 2 diabetes underwent fundoscopic examination by an ophthalmologist, and the factors that might be associated with the severity of retinopathy were investigated. Analysis of variance and the chi 2 test were performed to determine whether 22 separate factors were associated with the severity of diabetic retinopathy. There were significant associations between retinopathy and duration of disease, systolic blood pressure, urinary albumin index, and blood urea nitrogen. Multiple regression analysis with retinopathy as the criterion variable and 20 other factors as explanatory variables revealed that, of those explanatory variables showing statistical significance, the strongest associations were with duration of disease and type of diabetic therapy, in that order. The chi 2 test also revealed significant associations between retinopathy and both the type of diabetic therapy and the use of anti-hypertensive therapy. The results suggest that the duration of illness and the type of diabetic therapy are strongly related to the development and progression of retinopathy in patients with Type 2 diabetes. These findings suggest that insulin deficiency in patients with Type 2 diabetes should be corrected as early and as vigorously as possible, and that modification of daily activities to achieve a more nearly non-diabetic state should be instituted first, with supplementary drug therapy added as required.

Adolescent↗

PubMedDate not supplied

The effect of a very low dose of tolbutamide combined with an alpha-glucosidase inhibitor in non-insulin-dependent diabetes mellitus.

The effect of adding a very low dose of a sulphonylurea (tolbutamide) to the treatment of 10 patients with noninsulin-dependent diabetes mellitus (NIDDM) was investigated. Patients took 0.1 mg tds of an alpha-glucosidase inhibitor orally for 8 weeks, and 50 mg tds of the sulphonylurea, tolbutamide, for the last 4 weeks of this period. The glycosylated haemoglobin level was significantly reduced during the combined treatment period compared with the level after treatment with alpha-glucosidase inhibitor alone (P = 0.035), although not compared with the pretreatment level. There were no significant changes in post-prandial blood glucose, serum lipid levels or connective peptide immunoreactivities. These preliminary results indicate that the addition of a very low dose of tolbutamide to a recommended diet and treatment with an alpha-glucosidase inhibitor, may improve glucose metabolism without raising insulin secretion or influencing lipid metabolism.

Aged↗

PubMedDate not supplied

The effect of an alpha-glucosidase inhibitor and insulin on glucose metabolism and lipid profiles in non-insulin-dependent diabetes mellitus.

Studies were carried out to assess various ways of improving glycaemic control and lipid profiles of patients with noninsulin-dependent diabetes mellitus (NIDDM) in whom glucose metabolism was poor. Part or all of the dose of the sulphonylurea that had been used to treat patients in Group 1 (n = 8) was replaced by an alpha-glucosidase inhibitor. Symptoms related to hypoglycaemia disappeared and the postprandial blood glucose level was significantly increased (P < 0.043) but serum lipid levels were not significantly altered and the mean glycosylated haemoglobin level was unchanged. In Group 2 (n = 10) patients, a large part of the insulin dose was replaced by an alpha-glucosidase inhibitor. Hypoglycaemia-related symptoms disappeared but there were no significant changes in lipid profiles, postprandial blood glucose or glycosylated haemoglobin levels. The third group of patients (n = 9) had been treated with insulin alone and were given additional alpha-glucosidase inhibitor without changing their insulin dose. This did not significantly change their lipid profiles, postprandial blood glucose or glycosylated haemoglobin levels. In Group 4 (n = 9) the addition of an alpha-glucosidase inhibitor to the initial sulphonylurea did not produce any significant changes in mean postprandial blood glucose or glycosylated haemoglobin levels. The results for individual patients indicated that the glycosylated haemoglobin levels had improved after the change of treatment only in those patients whose connective peptide immunoreactivity was > or = 6.0 ng/ml.

Aged↗

PubMedDate not supplied

A novel monoclonal antibody, H9, directed against the core protein of MUC1 mucin.

MUC1 mucin is a target protein for many monoclonal antibodies. Human MUC1 detected by a murine anti-KL-6 monoclonal antibody that recognizes a sialylated carbohydrate chain has been designated KL-6/MUC1. Given the heterogeneous antigenicity of KL-6/MUC1, we established a new murine monoclonal antibody, H9, that reacts with epitope DTRP (Asp-Thr-Arg-Pro) peptides within the immunodominant region of the tandem repeat of MUC1 mucin. The reactivity of the H9 antibody differs from that of other previously reported antibodies that recognize the tandem repeat region of MUC1. Immunohistochemical experiments indicate that the reactivity of the H9 antibody is similar to that of other antibodies directed against MUC1 core proteins. A new cancer-associated protein detected by a sandwich assay using the H9 antibody as a catcher and the KL-6 antibody as a tracer is designated HK9. Serum HK9 levels showed a high expression level in lung cancer: 51% (19/37 cases) for adenocarcinoma, 39% (11/28 cases) for squamous cell carcinoma, and 67% (10/15 cases) for small cell carcinoma. The HK9 expression in lung cancer increased with cancer progression. These findings suggest monoclonal antibody H9 to be a novel antibody that reacts with an epitope within the tandem repeat region of MUC1, and that the cancer-associated antigen HK9 may have useful tumor-associated properties.

Animals↗

PubMedDate not supplied

Polyadenylation signal facilitates the expression of foreign gene that is driven by an internal promoter located in the reverse orientation to long terminal repeat of retrovirus.

We examined whether the presence of a polyadenylation [poly(A)] signal in a retrovirus vector could affect the expression level of exogenous gene(s) that was controlled by an internal promoter. Three suicide genes were placed under a promoter of the human midkine gene, whose expression is elevated in lung cancer cells. Orientation of the internal transcriptional unit was designed to be opposite to the viral long terminal repeat. Expression of each suicide gene was greater in ecotropic packaging cells transfected with a retrovirus vector without a poly(A) signal than in those with a poly(A)-containing vector. Sensitivity to ganciclovir, a prodrug that becomes an active drug by herpes simplex virus-thymidine kinase, was significantly improved in retrovirally transduced lung cancer cells compared with wild-type cells. However, the sensitivity was much greater in the cells transduced with poly(A)-containing vector than in those with poly(A)-deleted construct. The presence of a poly(A) signal downstream of exogenous gene(s) therefore favors the expression of foreign gene(s) driven by an internal promoter.

Biotransformation↗

PubMedDate not supplied

Tumor-specific chemo-radio-gene therapy for colorectal cancer cells using adenovirus vector expressing the cytosine deaminase gene.

We studied the effect of suicide gene therapy using an adenovirus vector expressing the cytosine deaminase (CD) gene combined with irradiation therapy (chemo-radio-gene therapy) for human colorectal cancer cells. Since serum CEA levels are elevated in patients with some malignant tumors including colorectal cancer, we applied the CEA promoter to chemo-radio-gene therapy, expecting tumor-specific expression of the CD gene. In in vitro study, we succeeded in selective expression of the target CD gene and growth inhibition in only CEA-producing tumor cells; Further the inhibitory effect was enhanced by combination with radiation therapy in an irradiation dose-dependent manner. In addition, in in vivo study, a significant growth inhibition was observed in chemo-radio-gene therapy in comparison with radiation therapy alone or suicide gene therapy alone. Thus, we suggest that tumor-specific chemo-radio-gene therapy may be a useful strategy for human colorectal cancer.

Adenocarcinoma↗

PubMedDate not supplied

Co-transduction of p27Kip1 strongly augments Fas ligand- and caspase-8-mediated apoptosis in U-373MG glioma cells.

BACKGROUND: p27Kip1 is a potential tumor suppressor gene. As malignant gliomas express Fas at high levels, the relationship between Fas-mediated apoptosis and p27Kip1 expression may improve therapeutic approaches for treating gliomas. MATERIALS AND METHODS: In this study, we transduced U-373MG glioma cells with the Fas ligand or caspase-8 genes using adenovirus vectors after transduction of the p27Kip1 gene to induce cell cycle arrest in U-373MG cells, and evaluated the degree of apoptosis. RESULTS: The results demonstrate that expression of p27Kip1 enhanced Fas ligand- or caspase-8-mediated apoptosis in U-373MG cells. Expression of apoptosis-related genes such as Bax, Bcl-X(L), Bcl-2 or caspase-8 were reduced by p27Kip1 transduction compared with that of beta-actin, whereas p27Kip1 transduction did not affect the expression level of Fas or the Fas ligand. CONCLUSION: Combined transduction of p27Kip1 with Fas ligand or caspase-8 would overide the resistance mechanism to apoptosis in malignant gliomas.

Adenoviridae↗

PubMedDate not supplied

[Activity of ATP-dependent protease and steroid metabolism in the human placenta].

Placenta play the important role of nourishment of fetus and for the regulation of fetal and maternal steroid metabolism. Steroid metabolism is synthesized in mitochondria and levels of enzymes in steroid metabolism are regulated by the rate of synthesis and degradation of these enzymes. Therefore, we studied protease in human placental mitochondria to clarify regulation mechanism of steroid-synthesizing enzymes. 50 micrograms of human early and term placenta homogenate, proteins were analyzed by immunoblotting technique after SDS-polyacrylamid gel electrophoresis. ATP-dependent protease was detected using antiserum raised against purified bovine adrenocortical ATP-dependent protease and avidin-biotin complex method. ATP-dependent protease activity was assayed using 14C-Caseins a substrate. Five cell fractions of homogenate placenta were electrophorated and antibody-stained using ATP-dependent protease, cytochrome P-450 scc and adrenodoxin antibody after the blotting, and the quantity was analyzed by the densitometry and the method of De Douve. We had the following results: 1) ATP dependent protease is present in human placenta and localized in mitochondria. 2) ATP dependent protease decomposes adrenodoxin reductase in human placenta. 3) ATP dependent protease present in almost same consistent in early and term placenta and there is no significant difference. It is suggested as follows that the ATP dependent protease in human placenta participates in the regulation of steroid hormone through the metabolism of steroid synthetic enzyme.

ATP-Dependent Proteases↗